a phase 3 study to evaluate the safety and efficacy of karxt + karx-ec for the treatment of agitation associated with alzheimer's disease (adagio-1)

Conditions: Alzheimer Disease

Summary: the purpose of this study is to evaluate the efficacy and safety of karxt + karx-ec in adult participants with agitation related to alzheimer's disease.


Eligibility criteria:
inclusion criteria: - a diagnosis of alzheimer's disease (ad) in accordance with the 2024 alzheimer's association criteria with one of the following confirmations of ad pathology:. i) historical evidence of ad diagnosis with amyloid positron emission tomography (pet), aβ42/40 ratio in csf, ptau181/aβ42 ratio in csf or ptau217/aβ42 ratio in plasma using an health authority (ha)-authorized diagnostic assay. ii) if no historical evidence available:. a. a plasma biomarker will be assessed for eligibility if allowed per regulatory requirements. the test cutoff(s) will be based on diagnostic use approval. b. if a plasma biomarker assay cannot be used or if the assay result is inconclusive, conduct one the following:. * amyloid pet. * aβ42/40 ratio or ptau181/aβ42 ratio in csf using an ha-authorized diagnostic assay. * mini-mental state examination (mmse) score of 5 to 22, inclusive, at screening (visit 1). * have one identified caregiver who should have sufficient contact (approximately 10 hours a week or more) and is willing to:. i) attend all visits and report on participant's status. ii) oversee participant compliance with medication and study procedures. iii) participate in the study assessments and provide informed consent to participate in the study. * history of agitation that meets the international psychogeriatric association (ipa) consensus definition for agitation in cognitive disorders with onset at least two weeks prior to screening (visit 1). * ad participants are required to have npi/npi-nh agitation/aggression score ≥ 4 at screening (visit 1) and baseline (visit 2). * cgi-s ≥ 4, as related to agitation, at screening (visit 1) and baseline (visit 2). * at least 1 of the following 3 criteria must be established from the cmai-ipa at screening (visit 1) and baseline (visit 2; cmai-ipa physical/verbal aggression positivity):. i) 1 or more aggressive behaviors occurring several times per week. ii) 2 or more aggressive behaviors occurring once or twice per week. iii) 3 or more aggressive behaviors occurring less than once per week. exclusion criteria: - medical conditions. i) agitation symptoms that are primarily attributable to a condition other than the ad causing the dementia. ii) history of bipolar disorder, schizophrenia, or schizoaffective disorder. iii) history of (or at high risk for) urinary retention, gastric retention, or narrow-angle glaucoma as evaluated by the investigator. iv) risk of suicidal behavior during the study as determined by the investigator's clinical assessment and/or c-ssr. - prior/concomitant therapy. i) recent history of receiving monoamine oxidase inhibitors, anticonvulsants (eg, lamotrigine, divalproex), mood stabilizers (eg, lithium), tricyclic antidepressants (eg, imipramine, desipramine), or any other psychoactive medications except for as needed anxiolytics (eg, lorazepam). a. selective serotonin reuptake inhibitors and serotonin norepinephrine reuptake inhibitors taken at a stable dose for at least 8 weeks prior to screening (visit 1) may be permitted. b. mirtazapine or trazodone may be used as a hypnotic if started at least 8 weeks prior to screening (visit 1). - other protocol-defined inclusion/exclusion criteria apply.